This invention relates generally to a device and method for generating particles and electromagnetic radiation that may be used for treating a variety of disorders, such as cancer, tumors and the like and in particular, to a device and method for utilizing neutrons to kill or damage tumor cells within the body of a patient.
There are various diseases in which undesirable cells grow within the body of a patient. These diseases include various types of cancers and other diseases in which a large mass of undesirable cells are formed in the body of the patient. To effectively treat these types of diseases, it is desirable to surgically remove as many of the undesirable cells as possible and then attempt by other means to damage or kill the cells remaining after the surgery. The most insidious of these diseases is cancer in which cells multiply uncontrollably in the body causing pain and the eventual death of the patient.
There are some forms of cancer which are particularly deadly in that they spread very rapidly, are located in places that make it difficult to operate and remove them and/or are nearly always fatal to the patient. One of these particularly deadly forms of cancer is a brain tumor. A brain tumor, once diagnosed, may typically kill the patient within a very short time frame. The five-year survival rate after the diagnosis of glioblastoma multiforme (one of the most frequent malignant brain tumor type) is less than 1%. Therefore, it is desirable to be able to extend the life expectancy of a person with a brain tumor and to improve the quality of life of the patient during the remaining time in his/her life. Many different treatments for various cancers, including brain tumors, have been developed that attempt to reduce the size of the tumor or eliminate the tumor entirely.
The treatment of these cancers may be conducted using non-radiation types of treatments. For example, chemotherapy may be used in which toxic chemicals are targeted at the cancer or tumor cells (using various well known techniques to target the tumor or cancer cells) so that the cancer or tumor cells are damaged or killed by the toxic chemicals. The problem with chemotherapy is that the toxic chemicals also tend to damage other cells or organ systems in the body, and have undesirable side effects, such as nausea, vomiting etc., which lead to a poor quality of life of the patient. For a brain tumor, the treatment typically involves surgery to debulk the tumor (remove as much of the tumor as possible without causing further damage to the healthy cells) followed by some other treatment to combat the cells remaining in the brain after the surgery. The treatment after the surgery may include various types of radiation treatment, as described below, which attempt to kill or damage the remaining cancer or tumor cells. The problem with this surgery and radiation treatment approach is that some brain tumors are inoperable and the radiation treatment alone does not sufficiently combat the tumor. Due to these limitations, other radiation or particle emitting treatments have been developed.
In the past, various types of radiation and particle emitting devices have been used for treating various diseases and maladies. The purpose of these devices is to destroy or disable the undesirable cells, such as tumor cells or cancer cells. To destroy or damage the undesirable cells, the particles or electromagnetic energy may strike and break the chemical bonds within the cancer cells so that these cells are destroyed. In any case, the radiation or particle energy must be highly focused on the tumor or cancer cells because the healthy cells surrounding the tumor or cancer cells are equally susceptible to radiation or particle damage. The goal, therefore, is to damage the cancer to tumor cells sufficiently with the radiation or particle energy to cause cell death while limiting the exposure of the healthy cells to the damaging particles and radiation. In particular, typical cells can repair some particle or radiation damage. Thus, the healthy cells with a more limited exposure than the tumor can repair the damage while the tumor or cancer cells cease functioning or die since they have been exposed to a larger dose of radiation or particles.
One typical technique for treating cancer or tumor cells is radiation treatment in which electromagnetic radiation is directed towards the tumor or cancer cells in order to damage the tumor or cancer cells. The radiation may be x-rays or other types of electromagnetic energy. The radiation is typically generated by a source outside the body, passes through the skin and tissue surrounding the tumor or cancer cells and is focused on the tumor or cancer cells so that a majority of the radiation energy is focused on the tumor or cancer cells. The problem with radiation treatment is that, to treat tumor or cancer cells inside of the body, the radiation must pass through surrounding healthy tissue which needs to be protected as much as possible from the radiation damage. Therefore, the amount of radiation energy that can be directed at the tumor cells during each treatment is limited by the amount of radiation that the surrounding healthy cells may be exposed to during each treatment. For example, if the dose to the surrounding healthy cells is too high, the healthy cells will also die which is undesirable. In addition, after a radiation treatment, the healthy surrounding cells must be given a chance to repair the damage before any further radiation treatment occurs. Therefore, due to the limited amount of radiation that may be directed to the tumor or cancer cells during each treatment and the period of time between each treatment to permit the healthy cells to repair, radiation treatments are delivered over many weeks. Thus, radiation treatment requires quite some time to damage the tumor or cancer cells sufficiently to kill them and may still cause a fair amount of damage to the surrounding healthy cells since the radiation must pass through the surrounding healthy cells.
Another typical technique for treating tumor or cancer cells is to use brachytherapy treatment in which a radiation source is inserted into or near the tumor so that the radiation from the radiation source is more focused into the tumor cells with less damage to the surrounding healthy cells. The radiation sources may include various elements that emit various types of radiation or particles including beta particles and gamma photons. Gamma photons and beta particles are referred to as low linear-energy-transfer (LET) radiation particles in which a particle transfers a small amount of its energy to a tumor cell on each passage. To be effective on cell killing, the small amount of energy transferred to each cell must be converted to free radicals via interacting with the oxygen existing in the cell. Therefore, a low LET radiation treatment is naturally ineffective to cancer cells that are hypoxic (have less oxygen than typical healthy cells). One type of hypoxic tumor cells are found in brain tumors.
Instead of these low LET radiation, it is also possible to use high LET radiation sources, such as neutrons. See R. A. Patchell et al., xe2x80x9cA phase I trial of neutron brachytherapy for the treatment of malignant gliomasxe2x80x9d, The British Journal of Radiology, Vol. 70, pp. 1162-1168 (November 1997). These neutron sources emit neutrons (a helium nucleus) which interact with the tumor cells to kill or damage them. A high LET radiation particle typically deposits a large fraction of its energy to a cell on each passage, and its cell killing effect is not affected by the amount of oxygen that is in the cells. Therefore, a neutron treatment is equally effective in killing or damaging both normal tumor cells and hypoxic tumor cells. The neutron source may be a radioactive element, such as californium (Cf), that may be internally placed near the tumor cells (i.e. the brachytherapy source) or an external neutron beam produced by a nuclear reactor or proton/deuteron accelerator. In a neutron therapy, neutrons typically interact with the tumor cells by colliding with hydrogen nuclei. The recoil hydrogen protons (i.e. protons) then break chemical bonds of the essential molecules (e.g. DNA) in the tumor cell and cause the tumor cell to be damaged and die.
The problem with typical brachytherapy neutron sources is that, although they may be inserted into a patient""s body, they are too large to be effectively used to treat patients. In particular, the large size of the source prevents the delivery of a desired neutron dose distribution within and around a tumor. The result is either an underdose to the tumor which renders the treatment ineffective, or an overdose to healthy tissues exemplified by the necrosis of the scalp and healthy brain tissues surrounding the tumor as noted in the article cited above. Another limitation with brachytherapy neutron sources is that the amount of californium that can be encapsulated in a source seed is too small so that the treatment time required is too long (xcx9c30 hours).
The problems with using an external neutron beam are that the beam is difficult to focus and that neutrons must past through healthy tissue to reach a tumor. These problems necessarily cause large unwanted doses of neutrons to the healthy tissues surrounding the tumor and thus limit the effectiveness of the treatment. In addition, either a nuclear reactor or an accelerator is much too expensive compared to conventional radiation sources.
There is yet another way of using neutrons to treat cancers, the so-called boron neutron capture therapy (BNCT). During a BNCT treatment, a compound containing boron-10 is injected into the patient""s bloodstream. Due to particular characteristics of the tumor cells, the boron compound is absorbed in greater amounts by the tumor cells than by the healthy cells surrounding the tumor. Then, the part of patient""s body that contains the tumor is exposed to an external low-energy (epithermal) neutron beam generated by a nuclear reactor (or an accelerator). The neutrons further slow down and reach thermal equilibrium in tissue. The xe2x80x9cthermalxe2x80x9d neutrons then interact with the boron-10 in the tumor cells to cause damage. That is, the capture of a thermal neutron by a boron-10 nucleus in a tumor cell instantaneously produces two energetic ions (a lithium ion and a helium ion). The two ions, in turn, break the chemical bonds of the essential molecules (e.g. DNA) and cause damage to the tumor cell. The problems of the BNCT are that equal amount of the boron compounds do not enter each tumor cell and that the boron content in tumor cells during a treatment cannot be determined accurately. Therefore, it is impossible to know precisely the neutron fluence necessary to kill the tumor cells. In addition, an epithermal neutron beam produces a thermal neutron field having its flux peaks at a depth between 2 to 5 cm in tissue. Therefore, it becomes less effective in treating deep seated tumors.
To overcome the above limitations and problems of conventional cancer and tumor treatments and devices, it is desirable to provide a new neutron brachytherapy device and method. It is to this end that the present invention is directed.
In accordance with the invention, a neutron brachytherapy device and method are provided which preferably use californium (252Cf) as the source to deliver neutrons directly to the tumor cells with minimal irradiation or damage to the healthy cells surrounding the tumor. A neutron from the source strikes the tumor cells and interact with the hydrogen in the cells to produce a charged hydrogen nucleus known as a recoil proton. The recoil proton then breaks chemical bonds of essential molecules (e.g. DNA) in the tumor cells and cause damages or deaths to the cells. The neutron source may be used alone or in combination with other treatments including, for example, boron neutron capture therapy (BNCT), surgery and conventional radiation treatments. The neutron source may be used to perform interstitial brachytherapy on tumors such as those occurring in the brain which generally have not responded to systemic therapy treatments. The neutron source in accordance with the invention has a higher radioactivity than the previously available neutron sources so that the total treatment time is significantly reduced. The neutron source in accordance with the invention also has a smaller size than the previously available neutron sources. The smaller size of the new source allows multiple sources to be more uniformly delivered and distributed within and around a tumor, and therefore provides more desirable dose distributions than the previously available sources.
The neutron source in accordance with the invention may include a neutron emitting radioactive material, such as Californium (252Cf) in a preferred embodiment, encased within a capsule. The capsule in accordance with the invention may permit the helium gas generated as the neutron source decays to be dissipated so that the capsule does not need to be periodically processed to release the helium gas. The capsule may be welded onto a guide wire to form a source wire so that the source wire and capsule may be inserted into the patient. The capsule may be a single or double walled design. The neutron emitting material may be loaded into the source wire in various ways as described below. The guide wire in accordance with the invention may be braided to strengthen and increase the flexibility of the source wire as well as to prevent the source wire from kinking.
To insert the neutron source into the patient, a catheter with a closed distal end may be inserted into the tumor by a surgeon using various techniques, such as stereotactic visualization and the like, to place the catheter. The closed end catheter prevents the patient""s fluids from contaminating the source wire. In accordance with the invention, there may be multiple catheters placed into the tumor depending on the dose distribution of the sources as well as the size and shape of the tumor. The catheters in accordance with the invention may be made of a flexible natural or synthetic material conventionally used in catheter manufacturing that is surrounded by a coiled metal wire. This prevents the catheter and source wire in the catheter from kinking and becoming lodged in the patient and increases the strength of the catheter. The metal coiled wire layer may be coiled around the catheter because the metal in the coiled wire does not affect the operation of the neutron source, whereas the operation of typical low LET radiation sources would be significantly affected by the metal coil wrapped around them. Once the catheters are placed in the appropriate locations in the tumor, a test wire without a radiation source is inserted into each catheter via a computer controlled remote delivery system called an xe2x80x9cafterloaderxe2x80x9d to ensure the source delivering process and then the test wire is removed. If successful, the source wire with the neutron source for each catheter is then loaded into each catheter to carry out the treatment.
Thus, in accordance with the invention, a neutron source for performing interstitial neutron brachytherapy is provided wherein the neutron source comprises a neutron emitting source material that is radioactive and decays while releasing helium gas and generating neutrons during the decay. The neutron source further comprises a capsule within which the neutron emitting source material is enclosed. The capsule walls do not interfere with the source neutrons and the capsule is sufficiently small so that multiple capsules can be simultaneously inserted into the body of a patient to treat the tumor. The neutron source further comprises a guide wire affixed to the capsule wherein the guide wire controlling the positioning of the capsule within the patient.